Verbal and visual dissociation in retrieval practice paradigm in neurodegenerative diseases

As is well known, prefrontal functions assert the control of inhibition for the retrieval of semantically related elements that lead to forgetfulness. The aim of this study is to document any verbal and visual dissociation in the Retrieval- Induced Forgetting (RIF). We want to test the hypothesis that representations in long-term visual memory are sufficiently rooted to be immune to impairment based on recognition, unlike oblivion induced by the retrieval of verbal material. The aim of this project is also to investigate which brain areas are most involved in the processes of inhibition and facilitation in patients with different types of cognitive impairment. To do this, 21 patients with Alzheimer's disease (AD), 21 mild cognitive impairment (MCI), 16 patients with subjective cognitive decline (SCD) and 23 healthy subjects (HS) were enrolled. All participants underwent an extensive neuropsychological evaluation by Addenbrooke's Cognitive Examination-Revised (ACE-R; Mioshi et al., 2006) and the Retrieval Practice Paradigm (RPP), with an experimental recognition task, where the same items were presented both in visual and verbal form to calculate, at a group level, the RIF and FAC (facilitation effect) effects. Only subjects who did not have contraindications to perform MRI, (14 AD, 16 MCI, 14 SCD and 18 HS) underwent 3 T-MRI scanning including a T1-w volume. Voxel-based morphometry (VBM) was used to assess associations between grey matter (GM) volumetrics and RPP indices: items practiced by practiced categories (Rp+), items which were not practiced, but were members of the same category as the Rp+ items (Rp-), items which received no additional retrieval practice and were not members of a practiced category (Nrp) in each group separately. ANOVA models were used to assess cross-sectional differences in all neuropsychological measures and experimental conditions and effects. In each of the 4 groups, separately, Pearson's correlations were used to assess potential association between each domain of ACE-R and the three RPP indices (Nrp, RP +, Rp-). Regarding the results about the RPP indices (Nrp, RP +, Rp-), for the verbal task, we observed a significant between-group difference in Nrp items. Post-hoc showed that the proportion of items in the Nrp condition is statistically higher in HS group than AD group. Moreover, we found a significant effect of group in Rp+ items: post-hoc revealed a significant difference between AD and SCD and between AD and HS. Interestingly, the tendency of significance was present on the comparison between AD and MCI. No significant differences were observed between MCI and SCD and between MCI and HS. Similarly, HS and SCD groups showed comparable performance on Rp+ items. Regarding the RPP effects (RIF and FAC), we observed a significant main effect of group in the FAC effect. Post-hoc revealed significant a main effect of group since AD recognized less items than SCD and HS, respetively. We found also a significant main effect of Condition, because the proportion of items retrieved in the Rp+ condition is statistically higher than that retrieved in the Nrp condition in all groups. Finally, we found no significant Group by Condition interaction indicating that the FAC effect was present in all considered groups. Finally, regarding the RIF effect, we observed a significant main effect of group, due to a significant difference exclusively between AD and HS groups; we revealed no significant effect of condition: indeed, in this case the means of item retrieved in two conditions Nrp and Rp- were almost the same. Finally, we found a significant Group by Condition interaction. The planned comparisons showed that the RIF effect was present in the SCD group only, but no RIF effect was observed in AD, in MCI and HS groups. For the visual task, no significant differences were observed between groups in the accuracy of the Nrp items, RP+ items, RP- items. As regards the FAC effect, we observed a significant main effect of group, due to a significant difference exclusively in the recognition of the global accuracy between AD and HS groups. We found also a significant main effect of Condition: in this case, the Rp+ items were better recalled than Nrp items in all groups. Finally, we observed no significant Group by Condition interaction, indicating that the FAC effect was present in all groups. Furthermore, about the RIF effect, in the verbal task, we observed no significant main effect of group, but significant main effect of Condition, since the Nrp items were better remembered than Rp- items. Moreover, we found no significant Group by Condition interaction: in this case, the planned comparisons revealed that the RIF effect was present in the SCD only. Comparing the groups individually, no significant dissociation emerged between two tasks, verbal and visual. There is only a tendency in SCD, due to greater accuracy of subjects who performed the verbal task, compared to those who performed the visual task, in the Rp- condition. For the MRI analysis results, in the Verbal task, VBM results showed in AD patients, revealed a positive association between Rp- items and GM volumes in the Right Putamen, Cingulus Gyrus and Left Putamen. In the Visual task the VBM analyses, revealed in AD patients a positive association between Nrp items and GM volumes in the Middle Frontal Gyrus, Inferior Frontal Gyrus, pars triangularis and Insular Cortex. Moreover, in SCD subjects, a significant positive association were found between Rp- items and GM volumes in the Postcentral Gyrus, Supramarginal Gyrus, Superior Frontal Gyrus, and Precuneous Cortex, bilaterally. In conclusion, in our study, in line with other experiments (Hogge et al., 2008; Saunders and Summers., 2011; Traykov et al., 2011; Ortega et al., 2012; Serra et al., 2022), shows the presence of an inhibitory effect: the RIF is not evident in the pathological group of AD and MCI, but not even in healthy subjects, which generally show good inhibition capacity; this result could be because the recognition task was too simple for healthy subjects, who were able to recall multiple items without distinction. Although there is a trend, in both tasks, in favor of a RIF effect as the pathology increases. We can also hypothesize that the worse performance observed in the RIF obtained from patients is not a direct expression of an inhibitory deficit but could depend on a general deficit of episodic long-term memory processes

In vivo mapping of brainstem nuclei functional connectivity disruption in Alzheimer's disease

We assessed here functional connectivity changes in the locus coeruleus (LC) and ventral tegmental area (VTA) of patients with Alzheimer's disease (AD). We recruited 169 patients with either AD or amnestic mild cognitive impairment due to AD and 37 elderly controls who underwent cognitive and neuropsychiatric assessments and resting-state functional magnetic resonance imaging at 3T. Connectivity was assessed between LC and VTA and the rest of the brain. In amnestic mild cognitive impairment patients, VTA disconnection was predominant with parietal regions, while in AD patients, it involved the posterior nodes of the default-mode network. We also looked at the association between neuropsychiatric symptoms (assessed by the neuropsychiatric inventory) and VTA connectivity. Symptoms such as agitation, irritability, and disinhibition were associated with VTA connectivity with the parahippocampal gyrus and cerebellar vermis, while sleep and eating disorders were associated with VTA connectivity to the striatum and the insular cortex. This suggests a contribution of VTA degeneration to AD pathophysiology and to the occurrence of neuropsychiatric symptoms. We did not find evidence of LC disconnection, but this could be explained by the size of this nucleus, which makes it difficult to isolate. These results are consistent with animal findings and have potential implications for AD prognosis and therapies

Influence of drug/lipid interaction on the entrapment efficiency of isoniazid in liposomes for antitubercular therapy: a multi-faced investigation

Hypothesis. Isoniazid is one of the primary drugs used in tuberculosis treatment. Isoniazid encapsulation in liposomal vesicles can improve drug therapeutic index and minimize toxic and side effects. In this work, we consider mixtures of hydrogenated soy phosphatidylcholine/phosphatidylglycerol (HSPC/DPPG) to get novel biocompatible liposomes for isoniazid pulmonary delivery. Our goal is to understand if the entrapped drug affects bilayer structure. Experiments. HSPC-DPPG unilamellar liposomes are prepared and characterized by dynamic light scattering, $\zeta$-potential, fluorescence anisotropy and Transmission Electron Microscopy. Isoniazid encapsulation is determined by UV and Laser Transmission Spectroscopy. Calorimetry, light scattering and Surface Pressure measurements are used to get insight on adsorption and thermodynamic properties of lipid bilayers in the presence of the drug. Findings. We find that INH-lipid interaction can increase the entrapment capability of the carrier due to isoniazid adsorption. The preferential INH-HSPC dipole-dipole interaction promotes modification of lipid packing and ordering and favors the condensation of a HSPC-richer phase in molar excess of DPPG. Our findings highlight the importance of fundamental investigations of drug-lipid interactions for the optimal design of liposomal nanocarriers.Comment: 28 pages (main manuscript + supplementary information

The beneficial effects of physical exercise on visuospatial working memory in preadolescent children

The relationship between physical exercise and improvement in specific cognitive domains in children and adolescents who play sport has been recently reported, although the effects on visuospatial abilities have not yet been well explored. This study is aimed at evaluating in school-age children practicing artistic gymnastics the visuospatial memory by using a table version of the Radial Arm Maze (table-RAM) and comparing their performances with those ones who do not play any sport. The visuospatial performances of 14 preadolescent girls practicing artistic gymnastics aged between 7 and 10 years and those of 14 preadolescent girls not playing any sport were evaluated in the table-RAM forced-choice paradigm that allows disentangling short-term memory from working memory abilities. Data showed that the gymnasts obtained better performances than control group mainly in the parameters evaluating working memory abilities, such as within-phase errors and spatial span. Our findings emphasizing the role of physical activity on cognitive performances impel to promote physical exercise in educational and recreational contexts as well as to analyse the impact of other sports besides gymnastics on cognitive functioning

Preclinical brain network abnormalities in patients with subjective cognitive decline

Alzheimer’s disease (AD) is the most common form of dementia worldwide. Currently there are no disease modifying treatments available. Detecting subjects with increased risk to develop dementia is essential for future clinical trials. Subjective cognitive decline (SCD) is a condition defining individuals who perceive a decrease in their own cognitive functioning in the absence of any detectable deficit on neuropsychological testing. SCD individuals show AD-related biomarkers abnormalities in cerebrospinal fluid. Objective:The aim of the present study was to assess brain functional connectivity (FC) changes in SCD individuals. Methods:23 SCD and 33 healthy subjects (HS) underwent an extensive neuropsychological assessment and 3T-MRI scanning including a T1-w volume and resting-state fMRI (RS-fMRI) to assess brain atrophy and brain FC. Results:No between-group differences in grey matter volumes were detected. SCD subjects compared to HS showed both increased and decreased FC in the executive and parietal networks. Associations between cognitive measures, mainly assessing working memory, and FC within brain networks were found both in SCD and HS separately. Conclusions:SCD individuals showed FC abnormalities in networks involving fronto-parietal areas that may account for their lower visuo-spatial working memory performances. Dysfunctions in executive-frontal networks may be responsible for the cognitive decline subjectively experienced by SCD individuals despite the normal scores observed by formal neuropsychological assessment. The present study contributes to consider SCD individuals in an early AD stage with an increased risk of developing the disease in the long term

Cognitive reserve modulates brain structure and cortical architecture in the Alzheimer’s Disease

Background:Cognitive reserve (CR) explains the individual resilience to neurodegeneration. Objective:The present study investigated the effect of CR in modulating brain cortical architecture. Methods:278 individuals [110 Alzheimer’s disease (AD), 104 amnestic mild cognitive impairment (aMCI) due to AD, 64 healthy subjects (HS)] underwent a neuropsychological evaluation and 3T-MRI. Cortical thickness (CTh) and fractal dimension (FD) were assessed. Years of formal education were used as an index of CR by which participants were divided into high and low CR (HCR and LCR). Within-group differences in cortical architecture were assessed as a function of CR. Associations between cognitive scores and cortical measures were also evaluated. Results:aMCI-HCR compared to aMCI-LCR patients showed significant decrease of CTh in the right temporal and in the left prefrontal lobe. Moreover, they showed increased FD in the right temporal and in the left temporo-parietal lobes. Patients with AD-HCR showed reduced CTh in several brain areas and reduced FD in the left temporal cortices when compared with AD-LCR subjects. HS-HCR showed a significant increase of CTh in prefrontal areas bilaterally, and in the right parieto-occipital cortices. Finally, aMCI-HCR showed significant positive associations between brain measures and memory and executive performance. Conclusion:CR modulates the cortical architecture at pre-dementia stage only. Indeed, only patients with aMCI showed both atrophy (likely due to neurodegeneration) alongside richer brain folding (likely due to reserve mechanisms) in temporo-parietal areas. This opposite trend was not observed in AD and HS. Our data confirm the existence of a limited time-window for CR modulation at the aMCI stage

I.S.Mu.L.T. Achilles Tendon Ruptures Guidelines

This work provides easily accessible guidelines for the diagnosis, treatment and rehabilitation of Achilles tendon ruptures. These guidelines could be considered as recommendations for good clinical practice developed through a process of systematic review of the literature and expert opinion, to improve the quality of care for the individual patient and rationalize the use of resources. This work is divided into two sessions: 1) questions about hot topics; 2) answers to the questions following Evidence Based Medicine principles. Despite the frequency of the pathology andthe high level of satisfaction achieved in treatment of Achilles tendon ruptures, a global consensus is lacking. In fact, there is not a uniform treatment and rehabilitation protocol used for Achilles tendon ruptures

Atrial electro-functional predictors of incident atrial fibrillation in cardiac amyloidosis

Background: Atrial fibrillation (AF) is common in patients with cardiac amyloidosis (CA) and is a significant risk factor for heart failure hospitalization and thromboembolic events. Objective: to investigate the atrial electro-functional predictors of incident AF in CA. Methods: A multicenter, observational study performed in 4 CA referral centers including sinus rhythm patients with light-chain (AL) and transthyretin (ATTR) CA undergoing electrocardiogram (ECG) and cardiac magnetic resonance (CMR). The primary endpoint was new-onset AF occurrence. Results: Overall, 96 patients (AL-CA: n=40; ATTR-CA n=56) were enrolled. During an 18-month median follow-up (Q1-Q3:7-29), 30 patients (29%) had incident AF. Compared with those without, patients with AF were older (79 vs 73 years, p=0.001) and more frequently with ATTR (73% vs 27%, p78 years showed a cumulative incidence for AF of 40% at 12 months. This risk was significantly higher than that carried by one (8.5%) or none (7.6%) of these three risk factors. Conclusions: In patients with CA, older age, IAB on 12-lead ECG and reduced LAEF on CMR are significant and independent predictors of incident AF. A closer screening for AF is advisable in CA patients carrying these features

Thalamocortical disconnection affects the somatic marker and social cognition: a case report

Thalamo-cortical connectivity was characterised in a patient with bilateral infarct of the thalami, without evidence of cognitive deficits in everyday life. Patient underwent social and emotional tests, Iowa Gambling Task (IGT), with and without concomitant heart rate variability (HRV) recording and at 3T-MRI to assess thalamo-cortical connectivity. Patient showed impairment at the IGT, in somatic marker, in emotions and theory of mind. MRI documented a bilateral damage of the centromedian-parafascicular complex. Patient's thalamic lesions disconnected brain areas involved in decision-making and autonomic regulation, affecting the somatic marker and resulting in the neuropsychological deficit exhibited by L.C

A new original nutraceutical formulation ameliorates the effect of Tadalafil on clinical score and cGMP accumulation.

Objective: To assess the efficacy of the combination of Tadalafil 5 mg and nutritional supplements composed by Panax ginseng, Moringa Oleifera and Rutin on erectile function in men with mild and moderate vasculogenic ED.Methods: we prospectively enrolled 86 patients divided into two groups A (45), B (33) in this multicenter randomized, doubleblind, placebo-controlled trial . Drop out was 8 patients (3 patients in group A and 5 in Group B). At screening visit patients underwent clinical examination, blood test (hormonal and metabolic profile) and filled out the IIEF-5 questionnaire and the SEP-2, SEP-3. Patients were randomized by a computergenerated list to receive either Tadalafil 5 mg once daily plus nutritional supplement once daily (group A) or Tadalafil 5 mg plus placebo with the same administration schedule (group B) for 3 months. Blood samples, IIEF-5, SEP-2 and SEP-3 have been collected again after 3 months. cGMP was measured in platelets of 38 patients at baseline and after one months. Results: Mean age was 59.98 ± 6.90 (range 38-69), mean IIEF-5 score at baseline was 13.59 ± 3.90. After three months of treatment, IIEF-5 score significantly improved in both groups compared to baseline (13.18 ± 3.75 vs 20.48 ± 2.24, p < 0.0001; 14.15 ± 4.09 vs 19.06 ± 4.36, p < 0.0001, in group A and group B respectively). Patients treated with Tadalafil plus nutritional supplement showed a significantly higher increase in IIEF-5 score compared to those who received placebo (7.27 ± 2.20 and 4.9 ± 2.79, respectively; p < 0.0001;). No hormonal differences and metabolic effects were found. According cGMP result, nutritional supplements ameliorates and extends the activity of the chronic treatment. Conclusions: IIEF-5 significant increase in group B, can be ascribed to the nutritional supplement properties and antioxidant effects of moringa oleifera, ginseng and rutin and this can enhance the endothelial NO and cGMP production